Contamination of autologous peripheral blood progenitor cell grafts predicts overall survival after high-dose chemotherapy in multiple myeloma.
BACKGROUND
Despite of the introduction of novel treatment modalities for multiple myeloma, high-dose chemotherapy with hematopoietic stem-cell rescue is still considered the standard of care for eligible patients <65 years of age. As we have previously reported, stem-cell grafts regularly contain quantities of plasma cells measurable by flow cytometry. However, the pathogenetic significance of this finding remains unknown.


METHODS
Multiple myeloma patients (n = 60) were mobilized with chemotherapy and filgrastim. Peripheral blood stem cell grafts were obtained by standard leukapheresis, and the number of CD38++/CD138+ cells/kg was determined by flow cytometry. Plasma cell contamination above a threshold of 4.5 x 10(5) plasma cells/kg was considered "high", whereas lower quantities of plasma cells or absent plasma cells in the graft were considered "low".


RESULTS
Progression-free survival: the median statistical progression-free survival was 33.5 months (range 11-99 months) in the high-contamination group (n = 16) versus 47 months (range 8-148 months) in the low-contamination group (n = 44). This difference turned out not to be statistically significant (P = 0.15). However, the difference was highly significant regarding overall survival with 53 months (range 11-119 months) in the high-contamination group and with 114 months (range 8-158 months) in the low-contamination group (P = 0.012).


CONCLUSIONS
Patients with >4.5 x 10(5) plasma cells/kg contaminating the peripheral blood stem cell graft received after high-dose chemotherapy have a significantly reduced overall survival. Whether high contamination of grafts with plasma cells might reflect residual in vivo tumor mass prior to stem cell transplantation and a generally more aggressive behavior of malignant myeloma cells in these patients, or whether reinfused plasma cells contribute to an unfavorable course of disease remains to be determined.
Kopp
H G
HG
Department of Medical Oncology, Hematology, Immunology, Rheumatology and Pulmology, Medical Center II, South West German Cancer Center, Eberhard-Karls-University, Tübingen, Germany. hans-georg.kopp@med.uni-tuebingen.de
Yildirim
S
S
Weisel
K C
KC
Kanz
L
L
Vogel
W
W
D051997:ADP-ribosyl Cyclase 1 / Q000032:analysis; D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000032:analysis; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D015415:Biomarkers / Q000032:analysis; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000627:therapeutic use; D015251:Epirubicin / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000473:pathology*; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery*; D009367:Neoplasm Staging; D016019:Survival Analysis; D053668:Syndecan-1 / Q000032:analysis; D014182:Transplantation, Autologous / Q000592:standards*; D055815:Young Adult
D015703:Antigens, CD; D015415:Biomarkers; D053668:Syndecan-1; D015251:Epirubicin; D005047:Etoposide; D003520:Cyclophosphamide; D051997:ADP-ribosyl Cyclase 1; D007069:Ifosfamide